The Maraviroc Central Nervous System (CNS) Study

October 15, 2019 updated by: Alan Winston, Imperial College London

The Penetration of Maraviroc Into the Central Nervous System in HIV-1 Infected Subjects on Stable Antiretroviral Therapy; a Phase I Pharmacokinetic Study

The purpose of this study is to describe the Central Nervous System exposure of maraviroc in HIV-1 infected subjects receiving a stable antiretroviral regimen, including maraviroc, at steady state.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

15 HIV-1 infected subjects currently receiving stable antiretroviral therapy will be recruited. At study entry, within 14 days of screening procedures, subjects will commence maraviroc dosed at 150 mg twice daily. For the rest of study period antiretroviral therapy will comprise:

  • Truvada™ one tablet once daily at 0900
  • Kaletra™ two tablets twice daily 0900 and 2100
  • maraviroc 150 mg twice daily at 0900 and 2100

Subjects will attend for regular clinic visits during study treatment phase.

On day 15, subjects will attend the unit in the morning prior to usual dosing time. Blood with be drawn to assess plasma maraviroc concentration pre dose and pre lumbar puncture. A lumbar puncture will be performed under standard aseptic techniques to asses CSF maraviroc concentration and routine CSF parameters.

On completion of this study visit, subjects will cease maraviroc, continue on their usual antiretroviral regimen and attend for a follow up visit 10 days later.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, W2 1NY
        • Imperial College Healthcare NHS Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • HIV-1 infected males or females
  • signed informed consent
  • plasma HIV RNA < 50 copies/mL at screening and on at least one other occasion over the last 3 months

  • currently receiving a stable antiretroviral regimen comprising of:

    • tenofovir 245 mg daily
    • emtricitabine 200 mg daily
    • a boosted protease inhibitor
  • no previous protease inhibitor resistance documented on HIV-1 genotypic resistance testing
  • Between 18 to 65 years of age, inclusive
  • subjects in good health upon medical history, physical exam, and laboratory testing

  • Female subjects who are heterosexually active and of childbearing potential (i.e., not surgically sterile or at least two years post menopausal) must practice contraception as follows from screening through completion of the study including 30 days following last dose of study drug:

    • barrier contraceptives (condom, diaphragm with spermicide)
    • IUD PLUS a barrier contraceptive
  • Female subjects of childbearing potential must have a negative pregnancy test.
  • Male subjects who are heterosexually active must use two forms of barrier contraception (e.g., condom with spermicide) during heterosexual intercourse, from screening through completion of the study including 30 days following last dose of study drug.
  • Have no serologic evidence of active HBV infection evidenced by negative hepatitis B surface antigen and no serologic evidence of hepatitis C virus infection by a HCV antibody or HCV PCR.
  • Have screening laboratory results (haematology, chemistry, and urinalysis) that fall within the normal range of the central laboratory's reference ranges unless the results have been determined by the Investigator to have no clinical significance

Exclusion Criteria:

  • current alcohol abuse or drug dependence
  • active opportunistic infection or significant co-morbidities including dementia
  • current prohibited concomitant medication (as listed in section 4.1.4)
  • Have a body mass index (BMI) > 32

  • Contraindication to lumbar puncture examination. Such as:

    • Existing neurological diseases
    • Bleeding disorders

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Maraviroc
Drug: Maraviroc
150mg twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CSF (Cerebrospinal Fluid) : Plasma Ratio of Maraviroc 1H Magnetic Resonance Spectroscopy (1H-MRS)
Time Frame: 15 days

To describe the CNS exposure of maraviroc in HIV-1 infected subjects receiving a stable antiretroviral regimen, including maraviroc, at steady state.

It were assessed by in vivo cerebral (1)H magnetic resonance spectroscopy ((1)H-MRS).

Cerebral MRS imaging (T1- and T2-weighted images) was performed on a Phillips Achieva™ 1.5 Tesla magnetic resonance (MR) scanner (Phillips NV, Best, Netherlands) and studied by an experienced neuroradiologist
15 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events
Time Frame: 15 days
To evaluate the short term safety and tolerability of maraviroc in HIV-1 infected subjects on stable antiretroviral therapy
15 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Imperial College London

Collaborators

Pfizer

Investigators

  • Principal Investigator: Alan Winston, Imperial College London

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2009

Primary Completion (Actual)

July 1, 2010

Study Completion (Actual)

February 1, 2011

Study Registration Dates

First Submitted

September 22, 2009

First Submitted That Met QC Criteria

September 22, 2009

First Posted (Estimate)

September 23, 2009

Study Record Updates

Last Update Posted (Actual)

November 4, 2019

Last Update Submitted That Met QC Criteria

October 15, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2008-008437-10

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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